Shilpa J, Paulose C S
Department of Biotechnology, Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin, 682 022, Kerala, India.
J Mater Sci Mater Med. 2014 Jul;25(7):1721-35. doi: 10.1007/s10856-014-5195-3. Epub 2014 Mar 30.
The metabolic alterations resulted from hepatic injury and cell loss lead to synaptic defects and neurodegeneration that undoubtedly contribute motor deficits. In the present study, GABA and 5-HT chitosan nanoparticles mediated liver cell proliferation influenced by growth factor and cytokines and neuronal survival in corpus striatum of partially hepatectomised rats was evaluated. Liver cell proliferation was initiated and progressed by the combined effect of increased expression of growth factor, insulin like growth factor-1 and decreased expressions of cytokines, tumor necrosis factor-α and Akt-1. This was confirmed by the extent of incorporation of thymidine analogue, BrdU, in the DNA of rapidly dividing cells. Inappropriate influx of compounds to corpus striatum resulting from incomplete metabolism elevated GABAB and 5-HT2A neurotransmissions compared to those treated with nanoparticles. This directly influenced cyclic AMP response element binding protein, glial cell derived neurotrophic factor and brain derived neurotrophic factor in the corpus striatum that facilitate neurogenesis, neuronal survival, development, differentiation and neuroprotection. Motor deficits due to liver injury followed striatal neuronal damage were scored by grid walk and rotarod studies, which confirmed the regain of motor activity by GABA and 5-HT chitosan nanoparticle treatment. The present study revealed the therapeutic significance of GABA and 5-HT chitosan nanoparticles in liver based diseases and related striatal neuronal damage that influenced by GABA and 5-HT.
肝损伤和细胞丢失导致的代谢改变会引发突触缺陷和神经退行性变，这无疑会导致运动功能障碍。在本研究中，评估了生长因子和细胞因子影响下的γ-氨基丁酸（GABA）和5-羟色胺（5-HT）壳聚糖纳米颗粒介导的肝细胞增殖以及对部分肝切除大鼠纹状体中神经元存活的影响。肝细胞增殖是由生长因子、胰岛素样生长因子-1表达增加以及细胞因子、肿瘤坏死因子-α和Akt-1表达降低的联合作用启动并推进的。这通过胸腺嘧啶类似物溴脱氧尿苷（BrdU）掺入快速分裂细胞DNA的程度得到证实。与纳米颗粒处理组相比，代谢不完全导致的化合物不适当流入纹状体，使GABAB和5-HT2A神经传递增加。这直接影响了纹状体中的环磷酸腺苷反应元件结合蛋白、胶质细胞源性神经营养因子和脑源性神经营养因子，这些因子有助于神经发生、神经元存活、发育、分化和神经保护。通过网格行走和转棒试验对肝损伤继发纹状体神经元损伤导致的运动功能障碍进行评分，结果证实GABA和5-HT壳聚糖纳米颗粒治疗可使运动活性恢复。本研究揭示了GABA和5-HT壳聚糖纳米颗粒在肝脏疾病及相关纹状体神经元损伤中的治疗意义，这些损伤受GABA和5-HT的影响。
